The capabilities of matrix assisted laser desorption ionization (MALDI) are considerably enhanced by introducing a high pressure ion mobility cell between the MALDI matrix target and an orthogonal time-of-flight mass spectrometer (OTOF/MS). Numerous advantages of this combination of instmments are demonstrated: MALDI ions are desorbed directly in the mobility cell at high pressures which allows ion pre-separation on a millisecond time-scale according to charge/volume ratio before entering the OTOF. The ionization/desorption process is decoupled from the OTOF, thus allowing both mass independent resolution and the application of pulse counting for increased sensitivity. The Phase II instrument will be more powerful than existing MALDI spectromcters and should become indispensable in simplifying and increasing the number of complex peptide mixture which can be identified. PROPOSED COMMERCIAL APPLICATION: The phase II instrument will lead the way to a new generation of MALDI instruments capable of analyzing more complex sample mixtures with a high throughput rate due to pre-separation on a millisecond time-scale.